Notch signaling and blood flow regulate vascular formation and maturation, but how shear stress affects the different components of the Notch pathway in endothelial cells is poorly understood. We show that laminar shear stress results in a ligand specific gene expression profile in endothelial cells (HUVEC). JAG1 expression increases while DLL4 expression decreases. Jagged1 shows a unique response by clustering intracellularly six to nine hours after the onset of flow. The formation of the Jagged1 clusters requires protein production, ER export and endocytosis. Clustering is associated with reduced membrane levels but is not affected by Notch signaling activity. Jagged1 relocalization is reversible, the clusters disappear and membrane levels increase upon removal of shear stress. We further demonstrate that the signaling potential of endothelial cells is enhanced after exposure to shear stress. Together we demonstrate a Jagged1 specific shear stress response for Notch signaling in endothelial cells.

中文翻译：

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剪切应力诱导 Jagged1 的表达、细胞内重组和增强的 Notch 激活潜力

Notch 信号传导和血流调节血管形成和成熟，但剪切应力如何影响内皮细胞中 Notch 通路的不同组成部分尚不清楚。我们发现层流剪切应力导致内皮细胞（HUVEC）中配体特异性基因表达谱。JAG1 表达增加，而 DLL4 表达减少。Jagged1 在流量开始后 6 至 9 小时在细胞内聚集，显示出独特的反应。Jagged1 簇的形成需要蛋白质生产、内质网输出和内吞作用。聚类与膜水平降低相关，但不受 Notch 信号活动的影响。Jagged1 重新定位是可逆的，剪切应力消除后，簇消失，膜水平增加。我们进一步证明，内皮细胞的信号传导潜力在暴露于剪切应力后增强。我们共同证明了内皮细胞中 Notch 信号传导的 Jagged1 特异性剪切应力响应。